Elevated NCOR1 disrupts a network of dietary-sensing nuclear receptors in bladder cancer cells

Increasingly invasive bladder cancer cells lines displayed insensitivity toward a panel of dietary-derived ligands for members of the nuclear receptor superfamily. Insensitivity was defined through altered gene regulatory actions and cell proliferation and reflected both reduced receptor expression and elevated nuclear receptor corepressor 1 (NCOR1) expression. Stable overexpression of NCOR1 in sensitive cells (RT4) resulted in a panel of clones that recapitulated the resistant phenotype in terms of gene regulatory actions and proliferative responses toward ligand. Similarly, silencing RNA approaches to NCOR1 in resistant cells (EJ28) enhanced ligand gene regulatory and proliferation responses, including those mediated by peroxisome proliferator-activated receptor (PPAR) gamma and vitamin D receptor (VDR) receptors. Elevated NCOR1 levels generate an epigenetic lesion to target in resistant cells using the histone deacetylase inhibitor vorinostat, in combination with nuclear receptor ligands. Such treatments revealed strong-additive interactions toward the PPARgamma, VDR and Farnesoid X-activated receptors. Genome-wide microarray and microfluidic quantitative real-time, reverse transcription-polymerase chain reaction approaches, following the targeting of NCOR1 activity and expression, revealed the selective capacity of this corepressor to govern common transcriptional events of underlying networks. Combined these findings suggest that NCOR1 is a selective regulator of nuclear receptors, notably PPARgamma and VDR, and contributes to their loss of sensitivity. Combinations of epigenetic therapies that target NCOR1 may prove effective, even when receptor expression is reduced.

Argyros Forum dedication

Dedication ceremony for Argyros Forum, with President James L. Doti speaking at the podium. George and Judi Argyros are on his right and Doy Henley seated at far right.

Dedication of the Pralle-Sodaro Residence Hall, chapman University, Orange, California

Dedication of the Pralle-Sodaro Residence Hall, 323 East Walnut Avenue, Chapman University, Orange, California, October 21, 1991. At the podium, George L. Argyros, Chairman of the Board of Trustees is speaking to Helga Pralle while President James L. Doti stands directly behind, and Bob Pralle applauds at right. Don and Dee Dee Sodaro are in the back at left. Pralle-Sodaro Hall (3 floors, 75,382 sq.ft.) is a three-story building containing one-hundred-fifty-five units. This state-of-the-art residence hall was made possible by the tremendous generosity of Bob and Helga Pralle and Don and DeeDee Sodaro. Bob Pralle served as a trustee for eighteen years beginning in 1984 and Don Sodaro as Chairman of the board of trustees and has served on the board for fourteen years beginning in 1988. Pralle-Sodaro Hall (3 floors, 75,382 sq.ft.) is a three-story building containing one-hundred-fifty-five units.

Transformación cultural en redes de cooperación empresarial

Ante la globalización y las nuevas tendencias de consumo que se han venido desarrollando a través de los años, las diferentes firmas en el mundo se han visto en la necesidad de buscar estrategias que les permita ser productivas generando más valor a los consumidores. En este sentido, ha surgido la necesidad de trabajar de manera conjunta y a su vez crear lazos de cooperación entre las diferentes organizaciones para el logro de mejores resultados. Las redes empresariales son una opción de integración de procesos y recursos para las organizaciones, sin embargo durante la creación de esta se generan cambios organizacionales que impactan en factores como la cultura organizacional. El cambio en la cultura organizacional se produce de manera gradual o abrupta según la forma de cooperación que ejecuten las empresas o por el contexto externo al cual pertenezca la organización. Así mismo, el líder es el encargado de gestionar el cambio en los valores (núcleo de la cultura), prácticas o la filosofía de las organizaciones; sin el apoyo de los líderes el fracaso de una cultura organizacional en una empresa, red, clúster o alianza será incuestionable.

Capacidad aeróbica de bomberos aeronáuticos

Los bomberos aeronáuticos son los encargados de atender todas las emergencias en los aeropuertos y sus cercanías. Estas emergencias incluyen emergencias aéreas, en tierra, eventos con materiales peligros e incendios, entre otros. Su trabajo tiene como características la realización de actividades durante periodos largos de baja intensidad y periodos cortos de alta intensidad. De acuerdo con estas características, es necesario que los bomberos aeronáuticos tengan una buena condición física. El consumo máximo de oxígeno (VO2 máx) como indicador de capacidad aeróbica resulta indispensable para conocer el desempeño de los bomberos en su trabajo. El objetivo de este estudio es determinar la capacidad aeróbica de los bomberos aeronáuticos y sus factores determinantes. Por tanto se desarrolló un estudio transversal de tipo descriptivo en una muestra de 23 hombres bomberos aeronáuticos. Se obtuvo información acerca de sus variables socio-demográficas, se determinó el VO2 máx y umbral ventilatorio mediante análisis de gases espirados durante un protocolo de ejercicio máximo sobre tapiz rodante, se evaluó la composición corporal mediante adipometría y se determinó el nivel de actividad física mediante el cuestionario internacional de actividad física IPAQ. Se encontró que la muestra tenia una edad de 32,6 ± 4,8 años, peso de 78,4 ± 9,8 kg, porcentaje de grasa de 14,8 ± 3,8 %, índice de masa corporal de 25,7 ± 2,7 y VO2máx de 44,6 ± 6. No se encontraron cambios significativos del VO2máx con la edad, pero si con la actividad física, porcentaje de grasa e índice de masa corporal. Se sugiere que el entrenamiento de los bomberos aeronáuticos durante su jornada laboral sea de intervalos de alta intensidad y que se monitorice su nivel de actividad física y composición corporal.

Diseño comunicaciones ltda. una gestión al servicio del liderazgo tecnológico

Analizar críticamente en función del desarrollo tecnológico la gestión realizada por DISEÑO COMUNICACIONES LTDA y formular propuestas sobre el manejo administrativo de los recursos tecnológicos para lograr el liderazgo en este campo,

El educando como sujeto y el lugar del juego en el debate educativo de finales del siglo XIX en Norteam??rica

El t??tulo aparece en espa??ol y, a continuaci??n, el t??tulo traducido al ingl??s: 'The Learner as Subject and the Place of Play and Games in the Educational Debate in North-America at the end of 19th Century'

The impact of age on the postprandial vascular response to a fish oil-enriched meal

Although chronic fish oil intervention had been shown to have a positive impact on vascular reactivity, very little is known about their acute effects during the postprandial phase. Our aim was to examine the impact of a fish oil-enriched test meal on postprandial vascular reactivity in healthy younger ( < 50 years) v. older ( ≥ 50 years) men. Vascular reactivity was measured at baseline (0 h), 2 and 4 h after the meal by laser Doppler iontophoresis and blood samples taken at 0 and 4 h for the measurement of plasma lipids, total nitrite, glucose and insulin. Acetylcholine- (ACh, endothelial-dependent vasodilator) and sodium nitroprusside (SNP, endothelial-independent vasodilator)-induced reactivities were greater at 4 h than at baseline or 2 h in the younger men (P < 0·04). These changes were not observed in the older men. Comparison of the male groups revealed significantly greater responses to ACh (P = 0·006) and SNP (P = 0·05) at 4 h in the younger compared with the older males. Postprandial NEFA concentrations were also greater at 4 h in the younger compared with the older men (P = 0·005), with no differences observed for any of the other analytes. Multiple regression analysis revealed age to be the most significant predictor of both ACh and SNP induced reactivity 4 h after the meal. In conclusion, the ingestion of a meal enriched in fish oil fatty acids was shown to improve postprandial vascular reactivity at 4 h in our younger men, with little benefit evident in our older men.

Fish oil fatty acids improve postprandial vascular reactivity in healthy men

Chronic fish oil intervention had been shown to have a positive impact on endothelial function. Although high-fat meals have often been associated with a loss of postprandial vascular reactivity, studies examining the effects of fish oil fatty acids on vascular function in the postprandial phase are limited. The aim of the present study was to examine the impact of the addition of fish oil fatty acids to a standard test meal on postprandial vascular reactivity. A total of 25 men received in a random order either a placebo oil meal (40 g of mixed fat; fatty acid profile representative of the U.K. diet) or a fish oil meal (31 g of mixed fat and 9 g of fish oil) on two occasions. Vascular reactivity was measured at baseline (0 h) and 4 h after the meal by laser Doppler iontophoresis, and blood samples were taken for the measurement of plasma lipids, total nitrite, glucose and insulin. eNOS (endothelial NO synthase) and NADPH oxidase gene expression were determined in endothelial cells after incubation with TRLs (triacylglycerol-rich lipoproteins) isolated from the plasma samples taken at 4 h. Compared with baseline, sodium nitroprusside (an endothelium-independent vasodilator)-induced reactivity (P = 0.024) and plasma nitrite levels (P = 0.001) were increased after the fish oil meal. In endothelial cells, postprandial TRLs isolated after the fish oil meal increased eNOS and decreased NADPH oxidase gene expression compared with TRLs isolated following the placebo oil meal (P <= 0.03). In conclusion, meal fatty acids appear to be an important determinant of vascular reactivity, with fish oils significantly improving postprandial endothelium-independent vasodilation.

Correction of atmospheric delay effects in radar interferometry using a nested mesoscale atmospheric model

The temporal variability of the atmosphere through which radio waves pass in the technique of differential radar interferometry can seriously limit the accuracy with which the method can measure surface motion. A forward, nested mesoscale model of the atmosphere can be used to simulate the variable water content along the radar path and the resultant phase delays. Using this approach we demonstrate how to correct an interferogram of Mount Etna in Sicily associated with an eruption in 2004-5. The regional mesoscale model (Unified Model) used to simulate the atmosphere at higher resolutions consists of four nested domains increasing in resolution (12, 4, 1, 0.3 km), sitting within the analysis version of a global numerical model that is used to initiate the simulation. Using the high resolution 3D model output we compute the surface pressure, temperature and the water vapour, liquid and solid water contents, enabling the dominant hydrostatic and wet delays to be calculated at specific times corresponding to the acquisition of the radar data. We can also simulate the second-order delay effects due to liquid water and ice.

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Wernicke’s aphasia occurs following a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used fMRI to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered following damage to the classical comprehension regions. Twelve participants with Wernicke’s aphasia and twelve control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and ROI analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an “over-activation” in comparison to control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results concord with models which indicate that the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions.

Mismatch Negativity (MMN) reveals inefficient auditory ventral stream function in chronic auditory comprehension impairments

Background: Auditory discrimination is significantly impaired in Wernicke’s aphasia (WA) and thought to be causatively related to the language comprehension impairment which characterises the condition. This study used mismatch negativity (MMN) to investigate the neural responses corresponding to successful and impaired auditory discrimination in WA. Methods: Behavioural auditory discrimination thresholds of CVC syllables and pure tones were measured in WA (n=7) and control (n=7) participants. Threshold results were used to develop multiple-deviant mismatch negativity (MMN) oddball paradigms containing deviants which were either perceptibly or non-perceptibly different from the standard stimuli. MMN analysis investigated differences associated with group, condition and perceptibility as well as the relationship between MMN responses and comprehension (within which behavioural auditory discrimination profiles were examined). Results: MMN waveforms were observable to both perceptible and non-perceptible auditory changes. Perceptibility was only distinguished by MMN amplitude in the PT condition. The WA group could be distinguished from controls by an increase in MMN response latency to CVC stimuli change. Correlation analyses displayed relationship between behavioural CVC discrimination and MMN amplitude in the control group, where greater amplitude corresponded to better discrimination. The WA group displayed the inverse effect; both discrimination accuracy and auditory comprehension scores were reduced with increased MMN amplitude. In the WA group, a further correlation was observed between the lateralisation of MMN response and CVC discrimination accuracy; the greater the bilateral involvement the better the discrimination accuracy. Conclusions: The results from this study provide further evidence for the nature of auditory comprehension impairment in WA and indicate that the auditory discrimination deficit is grounded in a reduced ability to engage in efficient hierarchical processing and the construction of invariant auditory objects. Correlation results suggest that people with chronic WA may rely on an inefficient, noisy right hemisphere auditory stream when attempting to process speech stimuli.

Future changes in the Western North Pacific tropical cyclone activity projected by a multidecadal simulation with a 16-km global atmospheric GCM

How tropical cyclone (TC) activity in the northwestern Pacific might change in a future climate is assessed using multidecadal Atmospheric Model Intercomparison Project (AMIP)-style and time-slice simulations with the ECMWF Integrated Forecast System (IFS) at 16-km and 125-km global resolution. Both models reproduce many aspects of the present-day TC climatology and variability well, although the 16-km IFS is far more skillful in simulating the full intensity distribution and genesis locations, including their changes in response to El Niño–Southern Oscillation. Both IFS models project a small change in TC frequency at the end of the twenty-first century related to distinct shifts in genesis locations. In the 16-km IFS, this shift is southward and is likely driven by the southeastward penetration of the monsoon trough/subtropical high circulation system and the southward shift in activity of the synoptic-scale tropical disturbances in response to the strengthening of deep convective activity over the central equatorial Pacific in a future climate. The 16-km IFS also projects about a 50% increase in the power dissipation index, mainly due to significant increases in the frequency of the more intense storms, which is comparable to the natural variability in the model. Based on composite analysis of large samples of supertyphoons, both the development rate and the peak intensities of these storms increase in a future climate, which is consistent with their tendency to develop more to the south, within an environment that is thermodynamically more favorable for faster development and higher intensities. Coherent changes in the vertical structure of supertyphoon composites show system-scale amplification of the primary and secondary circulations with signs of contraction, a deeper warm core, and an upward shift in the outflow layer and the frequency of the most intense updrafts. Considering the large differences in the projections of TC intensity change between the 16-km and 125-km IFS, this study further emphasizes the need for high-resolution modeling in assessing potential changes in TC activity.